Synthesis and Evaluation of a Chitosan Oligosaccharide-Streptomycin Conjugate against Pseudomonas aeruginosa Biofilms

Microbial biofilms are considerably more resistant to antibiotics than planktonic cells. It has been reported that chitosan coupling with the aminoglycoside antibiotic streptomycin dramatically disrupted biofilms of several Gram-positive bacteria. This finding suggested the application of the covalent conjugate of antimicrobial natural polysaccharides and antibiotics on anti-infection therapy. However, the underlying molecular mechanism of the chitosan-streptomycin conjugate (CS-Strep) remains unclear and the poor water-solubility of the conjugate might restrict its applications for anti-infection therapy. In this study, we conjugated streptomycin with water-soluble chitosan oligosaccharides (COS). Unlike CS-Strep, the COS-streptomycin conjugate (COS-Strep) barely affected biofilms of tested Gram-positive bacteria. However, COS-Strep efficiently eradicated established biofilms of the Gram-negative pathogen Pseudomonas aeruginosa. This activity of COS-Strep was influenced by the degree of polymerization of chitosan oligosaccharide. The increased susceptibility of P. aeruginosa biofilms to antibiotics after conjugating might be related to the following: Suppression of the activation of MexX-MexY drug efflux pump system induced by streptomycin treatment; and down-regulation of the biosynthesis of biofilm exopolysaccharides. Thus, this work indicated that covalently linking antibiotics to chitosan oligosaccharides was a possible approach for the development of antimicrobial drugs against biofilm-related infections.

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A Novel Water-Soluble Photosensitizer for Photodynamic Inactivation of Gram-Positive Bacteria

10.1101/2020.05.29.124768 ◽

2020 ◽

Author(s):

Zihuayuan Yang ◽

Ying Qiao ◽

Junying Li ◽

Fu-Gen Wu ◽

Fengming Lin

Keyword(s):

Photodynamic Therapy ◽

Water Solubility ◽

Uv Light ◽

Water Soluble ◽

Light Irradiation ◽

Microbial Fermentation ◽

Gram Positive ◽

Gram Negative ◽

Gram Positive Bacteria ◽

Uv Light Irradiation

AbstractAntimicrobial photodynamic therapy (APDT) is a promising alternative to traditional antibiotics for bacterial infections, which inactivates a broad spectrum of bacteria. However, it has some disadvantages including poor water solubility and easy aggregation of hydrophobic photosensitizers (PS), and poor tissue penetration and cytotoxicity when using UV as the light source, leading to undesired photodynamic therapy efficacy. Herein, we develop a novel water-soluble natural PS (sorbicillinoids) obtained by microbial fermentation using recombinant filamentous fungus Trichoderma reesei (T. reesei). Sorbicillinoids could effectively generate singlet oxygen (1O2) under ultraviolet (UV) light irradiation, and ultimately display photoinactivation activity on Gram-positive bacteria, but not Gram-negative ones. Staphylococcus aureus (S. aureus) treated with sorbicillinoids and UV light displayed high levels of intracellular reactive oxygen species (ROS), notable DNA photocleavage, and compromised cell semi-permeability without overt cell membrane disruption. Moreover, the dark toxicity, phototoxicity or hemolysis activity of sorbicillinoids is negligible, showing its excellent biocompatibility. Therefore, sorbicillinoids, a type of secondary metabolite from fungus, has a promising future as a new PS for APDT using nontoxic dose of UV light irradiation.ImportanceIt is of great value to develop novel PSs for APDT to enhance its efficacy for the reason that many traditional PSs have disadvantages like low water solubility and poor biocompatibility. In this study, we develop a novel water-soluble natural PS - sorbicillinoids obtained by microbial fermentation using T. reesei. Sorbicillinoids could effectively generate singlet oxygen under UV light irradiation, and ultimately display photoinactivation activity on Gram-positive bacteria, but not Gram-negative ones. More importantly, UV light can generally only be used to inactivate bacteria on the surface due to its weak penetration. However, it can penetrate deep into the solution and inactivate bacteria in the presence of sorbicillinoids. Therefore, sorbicillinoids, a type of secondary metabolite from fungus, has a promising future as a new PS for APDT using nontoxic dose of UV light irradiation.

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Novel Water-Soluble Photosensitizer for Photodynamic Inactivation of Gram-Positive Bacteria Using Nontoxic Dose of UV Light

10.21203/rs.3.rs-26136/v1 ◽

2020 ◽

Author(s):

Zihuayuan Yang ◽

Ying Qiao ◽

Junying Li ◽

Fu-Gen Wu ◽

Fengming Lin

Keyword(s):

Photodynamic Therapy ◽

Bacterial Infections ◽

Water Solubility ◽

Uv Light ◽

Water Soluble ◽

Light Irradiation ◽

Gram Positive ◽

Promising Alternative ◽

Gram Positive Bacteria ◽

Uv Light Irradiation

Abstract Background Antimicrobial photodynamic therapy (APDT) is a promising alternative to traditional antibiotics for bacterial infections, which inactivates a broad spectrum of bacteria. However, it has some disadvantages including poor water solubility and easy aggregation of hydrophobic photosensitizers (PS), and poor tissue penetration and cytotoxicity when using UV as the light source, leading to undesired photodynamic therapy efficacy.Results In this study, we develop a novel water-soluble natural PS (sorbicillinoids) obtained by microbial fermentation using recombinant filamentous fungus Trichoderma reesei (T. reesei). Sorbicillinoids could effectively generate singlet oxygen (1O2) under ultraviolet (UV) light irradiation, and ultimately display photoinactivation activity on Gram-positive bacteria, but not Gram-negative ones. Staphylococcus aureus (S. aureus) treated with sorbicillinoids and UV light displayed high levels of intracellular reactive oxygen species (ROS), notable DNA photocleavage, and compromised cell semi-permeability without overt cell membrane disruption. Moreover, the dark toxicity, phototoxicity or hemolysis activity of sorbicillinoids is negligible, showing its excellent biocompatibility.Conclusion Sorbicillinoids obtained from T. reesei display photoinactivation activity on Gram-positive bacteria using nontoxic dose of UV light irradiation and have an excellent biocompatibility Therefore, sorbicillinoids, a type of secondary metabolite from fungus, has a promising future as a new PS for APDT.

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Studies on the dehydrogenative polymerizations of monolignol β-glycosides. Part 2: Horseradish peroxidase-catalyzed dehydrogenative polymerization of isoconiferin

Holzforschung ◽

10.1515/hf.2006.085 ◽

2006 ◽

Vol 60 (5) ◽

pp. 513-518 ◽

Cited By ~ 13

Author(s):

Yuki Tobimatsu ◽

Toshiyuki Takano ◽

Hiroshi Kamitakahara ◽

Fumiaki Nakatsubo

Keyword(s):

Horseradish Peroxidase ◽

Water Solubility ◽

Homogeneous System ◽

Degree Of Polymerization ◽

Coniferyl Alcohol ◽

Water Soluble ◽

Optimum Conditions ◽

Spectroscopic Analyses ◽

Dehydrogenation Polymer ◽

Dehydrogenative Polymerization

Abstract Dehydrogenative polymerization of isoconiferin (IC; coniferyl alcohol γ-O-β-D-glucopyranoside) catalyzed by horseradish peroxidase (HRP) was carried out. The polymerization of IC proceeded in a homogeneous system, resulting in a water-soluble dehydrogenation polymer (IC-DHP). The degree of polymerization (DP) of IC-DHP was significantly higher than that of a standard dehydrogenative polymer (CA-DHP) obtained from coniferyl alcohol (CA) in a heterogeneous system. Under optimum conditions, the DP of IC-DHP was 44 (M n=1.5×104), whereas that for CA-DHP was only 11 (M n=3.0×103, as acetate). Spectroscopic analyses confirmed that IC-DHP has a lignin-like structure containing D-glucose moieties attached to the lignin side-chains. The D-glucose unit introduced into γ-O position of CA essentially influenced the water solubility and molecular mass of the resulting DHP.

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Novel Type of Water-Soluble Photosensitizer from Trichoderma reesei for Photodynamic Inactivation of Gram-Positive Bacteria

Langmuir ◽

10.1021/acs.langmuir.0c02109 ◽

2020 ◽

Vol 36 (44) ◽

pp. 13227-13235

Author(s):

Zihuayuan Yang ◽

Ying Qiao ◽

Junying Li ◽

Fu-Gen Wu ◽

Fengming Lin

Keyword(s):

Trichoderma Reesei ◽

Water Soluble ◽

Photodynamic Inactivation ◽

Gram Positive ◽

Gram Positive Bacteria

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In vitro activity of A-86719.1, a novel 2-pyridone antimicrobial agent.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.39.4.850 ◽

1995 ◽

Vol 39 (4) ◽

pp. 850-853 ◽

Cited By ~ 9

Author(s):

G M Eliopoulos ◽

C B Wennersten ◽

G Cole ◽

D Chu ◽

D Pizzuti ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Antimicrobial Agent ◽

Vitro Activity ◽

Pseudomonas Cepacia ◽

In Vitro Activity ◽

Gram Positive ◽

Xanthomonas Maltophilia ◽

Gram Positive Bacteria ◽

The Family

This study evaluated the in vitro activity of A-86719.1, a novel 2-pyridone antimicrobial agent. The drug inhibited all tested members of the family Enterobacteriaceae at < or = 0.5 microgram/ml and all tested Pseudomonas aeruginosa, Burkholderia (Pseudomonas) cepacia, and Xanthomonas maltophilia strains at < or = 2 micrograms/ml. All but two strains of gram-positive bacteria were inhibited by < or = 1 microgram of the new drug per ml, including isolates highly resistant to ciprofloxacin.

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Synthesis and characterization of water-soluble polyvinyl alcohol/pomegranate peel powder films

Biointerface Research in Applied Chemistry ◽

10.33263/briac103.484489 ◽

2020 ◽

Vol 10 (3) ◽

pp. 5484-5489

Keyword(s):

Contact Angle ◽

Water Contact Angle ◽

Water Solubility ◽

Barrier Properties ◽

Water Soluble ◽

Antibacterial Efficacy ◽

Pomegranate Peel ◽

Water Contact ◽

Gram Positive Bacteria ◽

Green Packaging

Biodegradable plastics had gained much attention among the researchers due to the arising of sustainability and environmental issues caused by petrochemical-based plastics. In this study, PVA films incorporated with pomegranate peel powder (PPP) were synthesized by using solution casting method. The effect of PPP on the surface morphology, physical properties, barrier properties and antibacterial activity of PVA based films were studied through FE-SEM, water solubility test, water contact angle test and Kirby-Bauer test. The incorporation of PPP had significantly enhanced the water solubility and surface energy of PVA-PPP films with the increasing of PPP content that caused reduction in water contact angle of the films. However, the films do not show a significant effect on the antibacterial efficacy against E.coli. In conclusion, PVA-PPP films have great potential to be used as green packaging materials for cosmetics products provided that further study on antibacterial efficacy against gram positive bacteria should be conducted.

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Medicinal Chemistry Updates on Bacterial Efflux Pump Modulators

Current Medicinal Chemistry ◽

10.2174/0929867325666180209142612 ◽

2019 ◽

Vol 25 (42) ◽

pp. 6030-6069 ◽

Cited By ~ 7

Author(s):

Fernando Durães ◽

Madalena Pinto ◽

Emília Sousa

Keyword(s):

Energy Source ◽

Antibiotic Resistance ◽

Efflux Pump ◽

Efflux Pumps ◽

The Other ◽

Drug Uptake ◽

Health Issues ◽

Gram Positive ◽

Gram Positive Bacteria ◽

Efflux Pump Inhibitors

Antibiotic resistance is one of the most pressing health issues of our days. It can arise due to a multiplicity of factors, such as target modification, decrease in the drug uptake, changes in the metabolic pathways and activation of efflux pumps. The overexpression of efflux pumps is responsible for the extrusion of drugs, making antibiotic therapy fail, as the quantity of intracellular antibiotic is not enough to provide the desired therapeutic effect. Efflux pumps can be included in five families according to their composition, nature of substrates, energy source, and number of transmembrane spanning regions. The ABC superfamily is mainly found in Gram-positive bacteria, use ATP as an energy source, and only a limited number of ABC pumps confer multidrug resistance (MDR). On the other hand, the MFS family, most present in Gram-positive bacteria, and the RND family, characteristic of Gram-negative bacteria, are most associated with antibiotic resistance. A wide variety of inhibitors have been disclosed for both families, from either natural or synthetic sources, or even drugs that are currently in therapy for other diseases. The other two families are the SMR, which are the smallest drug efflux proteins known, and the MATE family, whose pumps can also resort to the sodium gradient as an energy source. In this review, it is intended to present a comprehensive review of the classes of efflux pump inhibitors from the various sources, highlighting their structure-activity relationships, which can be useful for medicinal chemists in the pursuit of novel efflux pump inhibitors.

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Bacterial Profile and Antibiogram of Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia Patients in ICU of Raden Mattaher Hospital Jambi

INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY ◽

10.24293/ijcpml.v26i3.1596 ◽

2020 ◽

Vol 26 (3) ◽

Author(s):

Sotianingsih Sotianingsih ◽

Samsirun H. ◽

Lipinwati Lipinwati

Keyword(s):

Pseudomonas Aeruginosa ◽

Culture Media ◽

Sensitivity Test ◽

Sputum Culture ◽

Klebsiella Pneumonia ◽

Gram Negative Bacteria ◽

Gram Positive ◽

Acinetobacter Baumanii ◽

Gram Negative ◽

Gram Positive Bacteria

Pneumonia is defined as an inflammation of the lungs caused by microorganisms (bacteria, viruses, fungi, parasites). This research aimed to determine the pneumonia-causing bacteria along with the sensitivity and the antibiotic resistance test. This research was a descriptive study with samples of ICU pneumonia patients at Raden Mattaher Regional Hospital during the study period. All samples were consecutively selected. Samples for blood culture were incubated in the BactAlert device, whereas the sensitivity test was then performed using Vitex instruments. Sputum was previously enriched with BHI media and then cultured on culture media, and sensitivity test with the Vitex instruments was carried out. Of the 354 ICU patients during the study period, 30 patients (11.8%) had pneumonia, but only 19 patients could undergo sputum culture. Five of 19 patients were infected with Gram-positive bacteria, and 14 patients were infected with Gram-negative bacteria. The most commonly found bacteria were Klebsiella pneumonia (36.84%), followed by Acinetobacter baumanii (21.05%) and Pseudomonas aeruginosa (10.53%). Gram-negative bacteria obtained from sputum culture in this study were resistant to almost all antibiotic groups, especially penicillin, cephalosporin, quinolone, and tetracycline groups. Gram-positive bacteria obtained from sputum culture in this study were resistant to the penicillin antibiotic. The most commonly found bacteria were Klebsiella pneumonia (36.84%), followed by Acinetobacter baumanii (21.05%) and Pseudomonas aeruginosa (10.53%). The bacteria cultured from the sputum showed multidrug resistance mainly to the penicillin and cephalosporin antibiotic. This research data can be used to consider the treatment of pneumonia patients to decide more appropriate therapy.

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DefiningEscherichia colias a health-promoting microbe against intestinalPseudomonas aeruginosa

10.1101/612606 ◽

2019 ◽

Author(s):

Theodoulakis Christofi ◽

Stavria Panayidou ◽

Irini Dieronitou ◽

Christina Michael ◽

Yiorgos Apidianakis

Keyword(s):

Escherichia Coli ◽

Pseudomonas Aeruginosa ◽

Lactic Acid ◽

Wound Infections ◽

Human Gut ◽

Gram Positive ◽

E Coli ◽

Gram Positive Bacteria ◽

Intestinal Pathogens ◽

Health Promoting

AbstractGut microbiota acts as a barrier against intestinal pathogens, but species-specific protection of the host from infection remains relatively unexplored. Taking a Koch’s postulates approach in reverse to define health-promoting microbes we find thatEscherichia colinaturally colonizes the gut of healthy mice, but it is depleted from the gut of antibiotic-treated mice, which become susceptible to intestinal colonization byPseudomonas aeruginosaand concomitant mortality. Reintroduction of fecal bacteria andE. coliestablishes a high titer ofE. coliin the host intestine and increases defence againstP. aeruginosacolonization and mortality. Moreover, diet is relevant in this process because high sugars or dietary fat favoursE. colifermentation to lactic acid andP. aeruginosagrowth inhibition. To the contrary, low sugars allowP. aeruginosato produce the oxidative agent pyocyanin that inhibitsE. coligrowth. Our results provide an explanation as to whyP. aeruginosadoesn’t commonly infect the human gut, despite being a formidable microbe in lung and wound infections.Author SummaryHere we interrogate the conundrum as to whyPseudomonas aeruginosais not a clinical problem in the intestine as opposed to other tissues.P. aeruginosainteracts with Neisseria, Streptococcus, Staphylococcus and Actinomyces species found in the human lung. These are predominantly gram-positive bacteria that induceP. aeruginosavirulence. Moreover, peptidoglycan, which is abundant in gram-positive bacteria, can directly trigger the virulence ofP. aeriginosa. We reasoned thatP. aeruginosamight be benign in the human gut due to the inhibitory action of benign gram-negative intestinal bacteria, such asEscherichia coli. Therefore, we dissected the antagonism betweenE. coliandP. aeruginosaand the effect of a conventional, a fat-, a carbohydrate-and a protein-based diet in intestinal dysbiosis. Our findings support the notion that an unbalanced diet or antibiotics induces gut dysbiosis by the elimination of commensalE. coli, in addition to lactic acid bacteria, imposing a gut environment conducive toP. aeruginosainfection. Moreover, commensalE. coliprovides an explanation as to whyP. aeruginosadoesn’t commonly infect the human gut, despite being a formidable microbe in lung and wound infections.

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Identification of the microflora from the oral cavity of exotic snakes kepth as pets

Archives of Public Health ◽

10.3889/aph.2020.5272 ◽

2020 ◽

Vol 12 (2) ◽

pp. 56-63

Author(s):

Marko Naumovski ◽

Ivamaria Jovanovska ◽

Kakja Popovska ◽

Vesna Velikj Stefanovska ◽

Gordana Mirchevska

Keyword(s):

Pseudomonas Aeruginosa ◽

Oral Cavity ◽

Gram Negative Bacteria ◽

Proteus Vulgaris ◽

Gram Positive ◽

Providencia Rettgeri ◽

Gram Negative ◽

Gram Positive Bacteria ◽

Venomous Snakes ◽

The Republic

In recent years, snakes have become suitable pets for people with little spare time. By buying these animals people ignore the fact that they carry many microorganisms that are pathogenic for humans. The idea of this study was to identify the microorganisms from the oral cavity of exotic snakes kept as pets in the Republic of North Macedonia, which can help in the treatment of bite infections if they occur. The study comprised 30 snakes of 9 species, from 3 families of non-venomous snakes: Pythonidae, Boidae and Colubridae. Snakes are part of the 5 largest collections of exotic snakes in the Republic of North Macedonia. Only one swab from the oral cavity was taken from each snake. The brushes were cultured and microscopically analyzed at the Institute of Microbiology and Parasitology at the Faculty of Medicine in Skopje. From 59 isolated microorganisms from the oral cavity of 30 exotic snakes, 37.3% were Gram-positive bacteria, 61.01% were Gram-negative bacteria and 1.69% were fungi. Of the total number of microorganisms, Pseudomonas aeruginosa was predominant with 27.11%, Providencia rettgeri / Proteus vulgaris with 18.64% and KONS / Micrococcus luteus with 16.94%. Pseudomonas aeruginosa was present in all three snake families, with 62.5% of the snake in the fam. Pythonidae; 50% in the fam. Boidae and 50% in the fam. Colubridae. The isolate Providencia rettgeri / Proteus vulgaris was most frequently found in the fam. Colubridae with 71.43%, followed by fam. Pythonidae with 12.5%, but was not isolated in any specimen of the fam. Boidae. The microbiome of the non-venomous snakes is composed of Gram-positive bacteria in healthy snakes, but also in snakes kept in inadequate hygienic conditions. Gram-negative bacteria were predominant, of which the most significant was the presence of multiple drug resistance Pseudomonas aeruginosa. Snakes as pets require proper knowledge of terms and conditions.

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